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Diagnostic Performance of Different Pleural Fluid Biomarkers in Tuberculous Pleurisy

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Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 852))

Abstract

Due to the paucibacillary nature of tuberculous pleural effusion the diagnosis of pleural tuberculosis is challenging. This prospective study was undertaken to evaluate the diagnostic performance of ten different pleural fluid biomarkers in the differentiation between tuberculous and non-tuberculous pleural effusions. Two hundred and three patients with pleural effusion (117 men and 86 women, median age 65 years) were enrolled. Routine diagnostic work-up, including thoracentesis and pleural fluid analysis, was performed to determine the cause of pleural effusion. The following biomarkers were measured in pleural fluid: adenosine deaminase (ADA), interferon gamma (IFN-γ), interleukin 2 soluble receptor (IL-2sRα), sub-unit p40 of interleukin 12b (IL-12p40), interleukin 18 (IL-18), interleukin 23 (IL-23), IFN-γ induced protein 10 kDa (IP-10), Fas-ligand, human macrophage-derived chemokine (MDC) and tumor necrosis factor alfa (TNF-α). There were 44 (21.7 %) patients with tuberculous pleural effusion, 88 (43.3 %) patients with malignant pleural effusion, 35 (17.2 %) with parapneumonic effusion/pleural empyema, 30 (14.8 %) with pleural transudates, and 6 (3 %) with miscellaneous underlying diseases. Pleural fluid IFN-γ was found the most accurate marker differentiating tuberculous from non-tuberculous pleural effusion, with sensitivity, specificity, PPV, NPV, and AUC 97 %, 98 %, 95.5 %, 99.4 %, and 0.99, respectively. Two other biomarkers (IP-10 and Fas ligand) also showed very high diagnostic accuracy with AUC ≥ 0.95. AUC for ADA was 0.92. We conclude that IFN-γ, IP-10, and Fas-ligand in pleural fluid are highly accurate biomarkers differentiating tuberculous from non-tuberculous pleural effusion.

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References

  • Baumann MH, Nolan R, Petrini M, Lee YC, Light RW, Schneider E (2007) Pleural tuberculosis in the United States: incidence and drug resistance. Chest 131(4):1125–1132

    Article  PubMed  Google Scholar 

  • Budak F, Uzaslan EK, Cangur S, Goral G, Oral HB (2008) Increased pleural soluble fas-ligand (sFasL) levels in tuberculosis and its relation with T-helper type 1 cytokines. Lung 186(5):337–343

    Article  CAS  PubMed  Google Scholar 

  • Caulfield AJ, Lathem WW (2014) Disruption of Fas-Fas ligand signaling, apoptosis, and innate immunity by bacterial pathogens. PLoS Pathog 10(8):e1004252

    Article  PubMed Central  PubMed  Google Scholar 

  • Cui HY, Zhang O, Su B, Li W, Tang SJ (2010) Differential levels of cytokines and soluble Fas ligand between tuberculous and malignant effusions. J Int Med Res 38(6):2063–2069

    Article  CAS  PubMed  Google Scholar 

  • Daniil ZD, Zintzaras E, Kiropoulos T, Papaioannou AI, Koutsokera A, Kastanis A, Gourgoulianis KI (2007) Discrimination of exudative pleural effusions based on multiple biological parameters. Eur Respir J 30(5):957–964

    Article  CAS  PubMed  Google Scholar 

  • Dheda K, van Zyl-Smit RN, Sechi LA, Badri M, Meldau R, Meldau S, Symons G, Semple PL, Maredza A, Dawson R, Wainwright H, Whitelaw A, Vallie Y, Raubenheimer P, Bateman ED, Zumla A (2009a) Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis. Eur Respir J 34(5):1118–1126

    Article  CAS  PubMed  Google Scholar 

  • Dheda K, van Zyl-Smit RN, Sechi LA, Badri M, Meldau R, Symons G, Khalfey H, Carr I, Maredza A, Dawson R, Wainright H, Whitelaw A, Bateman ED, Zumla A (2009b) Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting. PLoS ONE 4(3):e4689

    Article  PubMed Central  PubMed  Google Scholar 

  • Gao ZC, Tian RX (2005) Clinical investigation on diagnostic value of interferon-gamma, interleukin-12 and adenosine deaminase isoenzyme for tuberculous pleurisy. Chin Med J 118(3):234–237

    CAS  PubMed  Google Scholar 

  • Giusti G (1974) Adenosine deaminase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic, New York, pp 1092–1099

    Chapter  Google Scholar 

  • Goto M, Noguchi Y, Koyama H, Hira K, Shimbo T, Fukui T (2003) Diagnostic value of adenosine deaminase in tuberculous pleural effusion: a meta-analysis. Ann Clin Biochem 40:374–381

    Article  CAS  PubMed  Google Scholar 

  • Greco S, Girardi E, Masciangelo R, Capoccetta GB, Saltini C (2003) Adenosine deaminase and interferon-γ measurements for the diagnosis of tuberculous pleurisy: a meta-analysis. Int J Tuberc Lung Dis 7(8):777–786

    CAS  PubMed  Google Scholar 

  • Guo SJ, Jia LQ, Hu QJ, Longm HY, Pangm CS, Wen FQ (2014) Diagnostic accuracy of interferon gamma-induced protein 10 for tuberculosis: a meta-analysis. Int J Clin Exp Med 7(1):93–100

    PubMed Central  PubMed  Google Scholar 

  • Jiang J, Shi HZ, Liang QL, Qin SM, Qin XJ (2007) Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis. Chest 131(4):1133–1141

    Article  CAS  PubMed  Google Scholar 

  • Kim YC, Park KO, Bom HS, Lim SC, Park HK, Na HJ, Park JH (1997) Combining ADA, protein and IFN-γ best allows discrimination between tuberculous and malignant pleural effusion. Korean J Intern Med 12(2):225–231

    CAS  PubMed  Google Scholar 

  • Krenke R, Korczynski P (2010) Use of pleural fluid levels of adenosine deaminase and interferon gamma in the diagnosis of tuberculous pleuritis. Curr Opin Pulm Med 16(4):367–375

    Article  CAS  PubMed  Google Scholar 

  • Krenke R, Safianowska A, Paplińska M, Nasiłowski J, Dmowska-Sobstyl B, Bogacka-Zatorska E, Jaworski A, Chazan R (2008) Pleural fluid adenosine deaminase and interferon gamma as diagnostic tools in tuberculous pleurisy. J Physiol Pharmacol 59(Suppl 6):349–360

    PubMed  Google Scholar 

  • Liang QL, Shi HZ, Wang K, Qin XJ (2008) Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med 102(5):744–754

    Article  PubMed  Google Scholar 

  • Light RW (2010) Update on tuberculous pleural effusion. Respirology 15(3):451–458

    Article  PubMed  Google Scholar 

  • Pai M, Flores LL, Hubbard A, Riley LW, Colford JM Jr (2004) Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis. BMC Infect Dis 4:6

    Article  PubMed Central  PubMed  Google Scholar 

  • Porcel JM (2009) Tuberculous pleural effusion. Lung 187:263–270

    Article  PubMed  Google Scholar 

  • Supryia P, Chandrasekaran P, Das SD (2008) Diagnostic utility of interferon-γ-induced protein of 10 kDa (IP-10) in tuberculous pleurisy. Diagn Microbiol Infect Dis 62(2):186–192

    Article  Google Scholar 

  • Trajman A, Kaisermann C, Luiz RR, Sperhacke RD, Rossetti ML, Féres Saad MH, Sardella IG, Spector N, Kritski AL (2007) Pleural fluid ADA, IgA-ELISA and PCR sensitivities for the diagnosis of pleural tuberculosis. Scand J Clin Lab Invest 67(8):877–884

    Article  CAS  PubMed  Google Scholar 

  • Trajman A, Pai M, Dheda K, van Zyl SR, Zwerling AA, Joshi R, Kalantri S, Daley P, Menzies D (2008) Novel tests for diagnosing tuberculous pleural effusion: what works and what does not? Eur Respir J 31(5):1098–1106

    Google Scholar 

  • Valdés L, San José E, Alvarez Dobaño JM, Golpe A, Valle JM, Penela P, González Barcala FJ (2009) Diagnostic value of interleukin-12 p40 in tuberculous pleural effusions. Eur Respir J 33(4):816–820

    Article  PubMed  Google Scholar 

  • Wang PS, Chen YM, Hsieh YL, Yu CF, Tsai CM, Perng RP (2002) Pleural effusion and serum soluble fas-ligand levels are elevated in different clinical conditions. Lung 180(1):25–32

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Yue J, Yang J, Gao R, Liu J (2012) Clinical diagnostic utility of adenosine deaminase, interferon-γ, interferon-γ induced protein of 10 kDa and dipeptidyl peptidase 4 levels in tuberculous pleural effusions. Heart Lung 41(1):70–75

    Article  PubMed  Google Scholar 

  • Wu SH, Li CT, Lin CH, Chu JJ, Cheng ML, Lin KH (2010) Soluble Fas ligand is another good diagnostic marker for tuberculous pleurisy. Diagn Microbiol Infect Dis 68(4):395–400

    Article  CAS  PubMed  Google Scholar 

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Correspondence to R. Krenke .

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Klimiuk, J., Krenke, R., Safianowska, A., Korczynski, P., Chazan, R. (2014). Diagnostic Performance of Different Pleural Fluid Biomarkers in Tuberculous Pleurisy. In: Pokorski, M. (eds) Respiratory Carcinogenesis. Advances in Experimental Medicine and Biology(), vol 852. Springer, Cham. https://doi.org/10.1007/5584_2014_105

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